Cytotoxic diterpenoid dimer containing an intricately caged core from Euphorbia fischeriana

Bislangduoids A and B, a novel class of dimeric diterpenoids based on ent-abietanes tethered by C-17-C-15' bridge, were identified as trace components from a traditional Chinese medicine Euphorbia fischeriana (Langdu). Bislangduoid A features a highly oxidized scaffold incorporating a cage-like pentacyclic core. Their structures were elucidated by extensive spectroscopic techniques, electronic circular dichroism, and NMR calculations. The biosynthetic pathway for the dimeric skeleton and the unique caged moiety via Michael and acetal-formation reactions was proposed. Bislangduoid A showed pronounced cytotoxicity against HepG2 cells through the mitochondria-dependent apoptosis pathway.